Targeted therapies in pediatric B-Cell acute lymphoblastic leukemia: mechanisms, efficacy, and future directions

Abstract

Background: Acute lymphoblastic leukemia (ALL) is the most common hematologic malignancy in children and is characterized by rapid progression and, in some cases, a high risk of relapse. Targeted therapies have revolutionized treatment with greater specificity, reduced systemic toxicity and a better prognosis. Objective: This review provides a comprehensive analysis of current targeted therapies for pediatric B-cell ALL, focusing on their mechanisms of action, efficacy, safety profiles, advantages, and remaining challenges. Methods: A systematic review of clinical trials published over the past 15 years was conducted. The analyzed therapies include monoclonal antibodies, antibody‒drug conjugates, tyrosine kinase inhibitors, proteasome inhibitors, and chimeric antigen–receptor T-cell (CAR-T cell) immunotherapy. Results: Targeted therapies improved progression-free survival and overall response rates, particularly in patients with relapsed/refractory ALL. CD19-directed CAR-T-cell therapy and bispecific antibodies (e.g., blinatumomab) have demonstrated high remission rates in early-phase clinical trials. Additionally, BCR-ABL1-positive ALL patients show benefit from tyrosine kinase inhibitors when combined with chemotherapy. Conclusion: Targeted therapies represent a paradigm shift in ALL treatments, enabling more personalized and effective strategies. Their integration into standard protocols, especially for high-risk and relapsed patients, is crucial to enhancing long-term outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251110522, identifier CRD420251110522